This invention is directed to a process of necrosing neoplasms as a result of hyperthermia of the neoplasm induced by hysteresis heating at selected frequencies of particles associated with the neoplasm.
It is a recognized medical fact that certain surgical invasions of neoplastic tumors in warm blooded animals can lead to adverse consequences. It is recognized that during the surgical removal of such neoplastic tumors, certain cells may be dislodged and entered into the general circulation of the war blooded animal to be carried to a distal site wherein an implantation of these cells occurs in the host. Growth of the neoplastic cells at the secondary site follows perpetuating the disease.
It is has further been recognized that if a neoplastic tumor could be destroyed without surgical intervention of the tumor site, the above described secondary spread of the neoplastic tumor would not occur. It is difficult enough to manage the metastasis of the tumor without further introducing secondary spread of the tumor by invasive surgical techniques.
Of the approaches taken to treat the tumor without surgical intervention of the same, the most common are radiation therapy and chemotherapy. While shortwave radiation such as X-rays and gamma rays are capable of destroying neoplastic tumors, they must, in fact, travel through overlaying body organs in order to reach the tumor site, and, if this form of radiation is not totally attenuated by the tumor, they will pass through further body organs beyond the tumor. The effect of the X-ray and gamma ray radiation on the normal body organs leads to serious side effects for this form of therapy.
Chemotherapy is also not without its side effects. The chemotherapeutic agent generally is distributed throughout the body of the warm blooded animal irrespective of its route of administration. It has been the goal of chemotherapy to develop chemotherapeutic agents which are only tumor specific acting agents and not agents which express their chemical effects on the general cellular population of the warm blooded animal. While strides have been made to develop agents which express their chemical effect on the more rapid growing tumor cells, other rapid growing body cells are also affected. This too leads to side effects in the use of these therapeutic agents.
It was suggested several decades ago to utilize hyperthermia to selectively destroy neoplastic tumors without concurrently destroying healthy tissue. Early attempts in this area involve surgical intervention into the tumor area of the warm blooded animal followed by hyperthermia treatment of the tumor site upon exposure of the same. Insofar as this technique involves surgical intervention into the body, aside from the necessity of a surgical procedure, it also potentially exposes the patient to dislodging of tumor cells and implantation of the same at secondary sites as discussed above. In order to circumvent surgical intervention into the body, induction heating hyperthermia has been explored.
In my prior U.S. Pat. No. 4,392,040, myself and my co-inventors thereof discuss certain hyperthermia procedures. Additionally, others, such as Borrelli et al, as is discussed in their U.S. Pat. No. 4,323,056, have explored this for control of neoplastic tumors. As is discussed in both of these two patents, both radio frequency and microwave frequency treatment have been explored.
Microwave radiation is utilized in diathermy. Unfortunately, the tissue of warm blooded animals is rather opaque to microwaves and the heating which results from exposure to microwaves occurs essentially at the body surface. Because of the attenuation of the microwaves by the body mass, little or no heating can be affected at deep seated points within the body cavity without excessive heating of the body surface. Because of this, hyperthermia treatment of imbedded neoplastic tumors is not possible without necrosing surface layers of the body.
In order to circumvent the above problems with prior known technologies, both myself and my co-inventors in my U.S. Pat. No. 4,392,040, Borrelli et al in the above referred to U.S. Pat. No. 4,323,056, and Gordon in U.S. Pat. No. 4,106,488 and U.S. Pat. No. 4,303,636 have suggested the use of hysteresis heating for deep seated neoplastic tumors. By exposing certain materials to magnetic fields, these materials can be heated. This heating ca be effected utilizing several mechanisms. First of these is hysteresis heating which results when these materials are positioned within an alternating magnetic field and results because of the hysteresis loss due to the varying magnetic flux on reversal of the field. The hysteresis heating is independent of particle size and, depending on the particular material, within a certain frequency range it is proportional to the frequency of the magnetic field.
A second type of heating is eddy current heating which results from current loops which are created in response to an alternating magnetic field. Eddy current heating is proportional to the electrical resistance of the conductor and is dependent upon particle size. It is further proportional to the frequency squared of the alternating magnetic field. It is known that eddy current heating can be reduced by reducing the particle size and, in fact, this technique is practiced in the electrical arts to reduce eddy current effects.
A further effect is encountered in treating biological specimens with alternating magnetic fields. This effect is dielectric heating which occurs in materials which are poor conductors. Dielectric heating results from reverse of polarization in the conductors in response to reversal of a high frequency electrical field.
As Borrelli stated in U.S. Pat. No. 4,323,056, the early implantation of powdered magnetic materials while demonstrative of the usefulness of localized induction heating to destroy neoplasms, was mitigated because of the heating of normal tissue and necrosis of the same due to dielectric heating resulting from the ionic conductivity of body tissue and fluids.
Because of the accompanying dielectric and/or eddy current heating of healthy tissue which accompanies hysteresis heating at higher frequencies, both myself and my co-inventors and Borrelli et al in U.S. Pat. Nos. 4,392,040 and 4,323,056, suggested the use of frequencies at, or below, 10 KHz, This serves to effectively eliminate destruction of healthy tissue resulting from concurrent dielectric and/or eddy current heating during hysteresis heating of metallic particles within a body.
I have found, however, that treatment of neoplastic tumors, utilizing hysteresis heating of particles within a body, at frequencies below 10 KHz, is also not without its qualifications. I have found, when warm blooded animals are placed within a coil as is described in my prior U.S. Pat. No. 4,392,040, and exposed to an alternating magnetic field in the frequency range described in that patent, and, further, as is included within the frequency range of the Borrelli et al U.S. Pat. No. 4,323,056, that the alternating magnetic field induces certain neuromuscular responses in the warm blooded animal, resulting in muscular movement and increase of muscular tone. This occurs because of the induction of minute amounts of current flow within the nerves controlling these muscles. Current flow in the nerves leads to muscle tonic and clonic contractions. This is extremely painful and, further, this condition can lead to intramuscular bleeding with the breakdown of the myosin in the muscle. The myosin can then be transported to the kidney wherein it clogs the kidney leading to kidney failure and death.
In order to circumvent the neuromuscular response, it is necessary to concurrently administer a muscular blocking agent such as curare. Curare is a general muscle relaxant and, as such, also expresses its effect on the lungs. Because of this it is necessary to anesthetize the patient under a general anesthesia and place the patient on a respirator in order to affect breathing until such time as the muscle relaxant state is removed.